RT Journal Article
SR Electronic
T1 Chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 510396
DO 10.1101/510396
A1 Erik J. Vrij
A1 Yvonne S. Scholte op Reimer
A1 Javier Frias Aldeguer
A1 Isabel Misteli Guerreiro
A1 Jop Kind
A1 Bon-Kyoung Koo
A1 Clemens A. van Blitterswijk
A1 Nicolas C. Rivron
YR 2019
UL http://biorxiv.org/content/early/2019/04/12/510396.abstract
AB The early mammalian conceptus (blastocyst) contains two supporting extraembryonic tissues - the trophectoderm and the primitive endoderm (PrE) - that encase and guide the epiblast (Epi) to eventually form the all body. Modifications of the conceptus exposed key genes regulating these tissues co-development. However, the combinations of signalling pathways underlying the interplay of PrE and Epi remains elusive. Stem cell-based models including embryoid bodies and blastoids can be generated in large numbers and subjected to high-content screens. Here, we use combinatorial screens of proteins, GPCR ligands and small molecules to rapidly (72 hours) and efficiently (80%) guide embryoid bodies to form a three-dimensional PrE-/Epiblast-like niche in chemically-defined conditions (gel-free, serum-free). This bipotent niche spontaneously progresses, without growth factors, to form a pro-amniotic cavity surrounded by a polarized Epi covered with parietal and visceral endoderm-like cells. In blastoids, these molecules enhance the ratio and number of Gata6+/Nanog+ cells and promote the survival, expansion and morphogenesis of a post-implantation-like Epi in vitro. Altogether, modelling early development in chemically-defined conditions delineates the pathways sufficient to form a functional PrE/Epiblast niche that fuels post-implantation development.